Multivitamin compositions



Patented June 3, 1947 OFFICE MULTIvi'rAMm comosrrrons Loran Oid Bu'xton,East Orange, and Sol Tobias Lipeins, Orange, N. J., assignors to NopcoChemical Company, a corporation of New Jersey No Drawing. ApplicationOctober 28, 1942, Serial No. 463,664

. l This invention relates to vitamin compositions and more particularlyto multi-vitamin composi-.

tions dispersible in aqueous media and to correlated improvements inprocesses for preparing I said compositions.

The presently known vitamins may be grouped into two generic classes,fat-soluble vitamins and Water-soluble vitamins. Concentrates offat-soluble vitamins, e. g., vitamins A, D and E concentrates, areordinarily sold in the form of solutions of the vitamins in the oils inwhich they occur naturally or in other oils in which they are-dissolved;Such solutions of vitamins, however, cannot be readily incorporated intoaqueous bodies since they are immiscible therewith; this property isdisadvantageous since it is highly desirable to incorporate fat-solublevitamins into many aqueous iood products and medicinal preparations suchas milk, tonics and the like. Also in many cases it is highly desirableto have aqueous food products and the like containing substantially allof the vitamins, both fat-soluble and water-soluble, e. g., it would bevery desirable indeed to have a milk containing substantially all ofthevitamins in such quantities that a pint or a quart thereof wouldsupply all of a persons normal daily requirements. It can readily beseen that it is quite a complex problem to produce a satisfactory,stable, concentrated composition containing substantially all of thevitamins and which is completely water-dispersible in an aqueous mediumto give a productcontainin'g sub stantially all of the vitamins with'thevitamins being present therein in substantial amounts and in theirproper proportions for supplying the body's needs. In the first place,the two major classes of the vitamins, i. e., the fat-soluble and thewater-soluble, have widely. divergent physical and chemicalcharacteristics; furthermore, the individual vitamins are quite variedin their properties which further complicates the problem. Also, inorder to produce a commercially practicable product, it is essentialthat the composition be quite concentrated; otherwise, in order toobtain the desired vitamin potency in the aqueous food product, such alarge amount of the vitamin composition would have to be added theretothat in all probability the characteristics, 1. e., taste,

, color, odor, etc., of the aqueous food product would be affectedthereby. Our 'copending application, Serial No. 282,128,

filed June 30, 1939, now Patent No. 2,311,517, de-,

scribes a process for producing a wate'r-dispersible compositioncontaining tat-soluble and water-soluble vitamins. While the productdescribed in 4 Claims. (Cl. 167-81) the aforesaid application hasenjoyed commercial success, some dimculty has been encountered inincorporating certain of the water-soluble vitamins into thecomposition. Particular difllculty has been encountered with riboflavinand vitamin C as these vitamins are very sparingly soluble in water andaqueous alcoholic solutions.

It is the object of this invention to provide improved stablewater-dispersible multivitamin compositions containing both fat-solublevita-.

mins and water-soluble vitamins.

Another'object of this invention is to provide an improved process forpreparing stable waterdispersible multi-vitamin compositions.

Still another object of this invention is-to provide a stablewater-dispersible emulsion 01. substantially all of the vitaminsnormally ingested.

A further object of this invention is to provide a stablewater-dispersible multivitamin composition of such a potency that onecubic centimeter or less will supplysubstantially all of the averagedaily vitamin requirements of an individual.

Another object of this invention is to provide milk and other aqueousfood products containing all of the vitamins in the properproportionsfor supplying the body's needs.

Another object of this invention is toprovide dispersions of bothwater-soluble and fat-soluble vitamins in aqueous media wherein thevitamins will remain highly stable at elevated temperatures. a

Other objects of the invention will in part be obvious and win in partappear hereinafter.

We have found that excellent, stable, completely water-dispersiblemultivitamin composi-- tions containing both fat-soluble vitamins andwater-soluble vitamins can be readily and easily prepared byincorporating the vitamins; into a solvent comprising ethyl alcohol anda blending solvent selected from the group consisting of glycerineand/or lactic acid. Such multi-vitamin compositions can be easilydispersed in aqueous media so as to produce relatively clear dispersionsof high vitamin potencies without any separation of the oily fat-solublevitamin concentrates. In these vitamin compositions the fat-solublevitamin concentrates are already in somewhat of a dispersed stateinstead of entirely in solution as is the case in the compositions ofthe application hereinabove mentioned. The ease of dispersion of thevitamin compositions is thus increased by the fat-soluble vitamins beingin such a dispersed state, and also the stability of the resultingvitamin-fortified aqueous product appears to be enhanced thereby.Furthermore,

the presence of the glycerol and/or lactic acid increases thecompatibility of the vitamin com position with certain food products.The glycerol and/or lactic acid make the compositions of the inventionsomewhat more viscous than a solution of the vitamin in ethanol alone,and because of this increased viscosity, vitamins which are susceptibleto oxidative deterioration, e. g., vitamins A and C, are more stabletherein than in the ethanol solutions, since in the more viscoussolutions there will be less surface area coming in contact withoxidizing influence during handling and shipping of the vitamincompositions. The most significant advantage of the presence of glyceroland/or lactic acid is that compositions of considerably higher potenciesin vitamin C and riboflavin can be obtained, since it has been foundthese vitamins have much greater solubility in glycerol and/or lacticacid and mixtures thereof with ethanol than in ethanol alone. This isparticularly true in the case of riboflavin as it is only very slightlyoluble in ethanol. Glycerine" and lactic acid serve as blending solventsin the composition of the invention. Another advantage of thecompositions of this invention is that they are less volatile thancompositions in which ethanol is used alone, and there is thus much lesslikelihood of any undesirable changes taking place in the physicalcharacteristics of the vitamin composition through loss of solvent byevaporation. The vitamin compositions of our invention may be permittedto stand for long periods of time without substantial deterioration inthe vitamin potencies thereof; this property is highly desirable sincethe compositions may thus be stored and shipped as desired withoutdanger of a substantial deterioration in their vitamin potencies. Inactual storage tests on the vitamin compositions we have found thatafter periods of as long as six months, no appreciable deterioration ofthe vitamins therein takes place. Aqueous dispersions of themultivitamin compositions may be prepared by merely mildly agitating thecompositions with an aqueous body. These dispersions are capable ofstanding for long periods of time without breaking. Also they areparticularly stable at elevated temperatures, e. g., temperatures in theorder of the boiling point of water; this factor is of great advantagein the preparation of many food products, since it permits the vitaminsto be readily incorporated into food products during cooking or otherhigh temperature operations. By the process of our invention completelywater-dispersible products can be prepared which contain substantiallyall of the vitamins in the proper ratio for supplying the body's needsand in such a concentration that a very mall amount thereof will supplythe average daily needs of an individual. For example compositions maybe prepared such that when amounts as small as one-half cc. are addedtoa pint of milk or skim milk, the milk will supply substantially all ofthe average daily vitamin requir ments of an individual.

The fat-soluble vitamin concentrates which are used in preparing themultivitamin compositions of our invention may be any suitable vitaminor provitamin concentrate or concentrates of vitamins A, D, or E;however, it is preferred that relatively highly potent concentrates ofthese vitamins be used. Thus, for example, vitamin A concentratescontaining from about 300,000 to about 2,500,000 A units per gram,preferably from about 750,000 to 2,500,000 A units per gram, and

vitamin D concentrates containing from about 100,000 to about 2,000,000D units per gram, preferably from about 500,000 to about 2,000,000 Dunits per gram, may be employed. Mixed A and D concentrates containingfrom about 800,000 to about 1,800,000 A units per gram and from about100,000 to about 1,400,000 D units per gram may also be utilized. Theconcentrates may be prepared in any suitable manner; for example,vitamin A or D concentrates prepared from fish oils, caroteneconcentrates and vitamin D concentrates obtained by irradiating orotherwise activating sterols, e. g., cholesterol, ergosterol, 'l-dehydrocholesterol, etc., or oil solutions thereof, may be employed.Preferably, the vitamin A or D concentrates are prepared bysaponification of fish liver oils and extraction of the unsaponifiedportion with a suitable solvent since these concentrates are relativelyinexpensive and form excellent dispersions in aqueous media whenemployed in the practice of our invention. It is preferred to employhigh potency fat-soluble vitamin concentrates from which the portioninsoluble in methanol or ethanol at relatively low temperatures has beenremoved; such high potency concentrates may be obtained by dissolving afatsoluble vitamin'concentrate in methanol or ethanol at roomtemperature, then cooling the solution to a relatively low temperature,e. g., about -20 C., and separating the insoluble portion (cholesterol,etc.) from the solution. Multivitamin compositions prepared by theprocess of our invention using such concentrates can be dispersed inaqueous bodies with great ease to give highly desirable fortifiedproducts.

The water-soluble vitamins which are employed in the process of ourinventionmaybe either concentrates of the naturally-occurring forms ofthe vitamins or products which have been produced synthetically. Thusmembers of the vitamin .B complex may be added as natural con centratesprepared from materials suchas rice bran, rice polishings, milk whey,etcqorithey may be added as synthetic materials such 'as thiaminhydrochloride, synthetic riboflavin, synthetic nicotinic acid amide(niacin), synthetic pantothenic acid or calcium pantothenate, etc.Likewise, the vitamin C employed may be a natural concentrate or thesynthetic product.

In carrying out the preferred process of our invention, the desiredamounts of the water-soluble vitamins are thoroughly mixed with theglycerine and/or lactic acid until a homogeneous mass is obtained. Thismass is diluted with ethanol and the fat-soluble vitamins are addedthereto in an ethanol solution thereof. If desired, the fat-solublevitamin concentrates may be add: ed directly to the solution of ethanoland glycerine and/or lactic acid instead of first dissolv ing them inethanol. Of course, other obvious variations in the order or manner ofthe incorporation of the vitamins into the solvents may be employed.Thus the water-soluble vitamins may be added directly to a mixture ofethanol and glycerine and/or lactic acid either before 0'1" afterfat-soluble vitamins have been added The relative proportions ofethanol,

thereto. glycerol, and lactic acid may vary considerably, but it ispreferred that ethanol comprise at least about 50 parts and not morethan about parts of every hundred parts of the dispersible vitamincompositions. The amount of lycerine which is used may be as high asabout '50 parts for every hundred parts of the vitamin compositions, butin the case of the lactic acid it is preaferrednottousemorethanabouttopartspereveryhundredpartsoftheflnaldisperslhleproduct.Piei'erablyJthanolshouldcomprlseatleast about65%ofthevitamincomposition. After all or thevitamins have been incorporatedtherein. the solutionisthoroughlymixedtoinsurethe uniform distribution.of the vitamins Estimates of the amounts of the diiferent vitaminsrequired hy-an individual varyJiut figuresgiveninatableputoutbytheUniversityof Wisconsin Experiment Station arerepresentative of most recent findings According to this table anindividual should receive each day from 3000 to6000InternationalunitsofvitaminA,from 250 to 300 International units of vitamin 131.about 500 International units of vitamin 0, about ,400 Internationalunits of vitamin D (for children:

adults do not require quite that much), 10 to mg. of nicotinamide(niacin amide), and 1 to 2 mg. of vitamin G (riboflavin). In preparingour multivitamin compositions,' we prefer in most cases to incorporatetherein suilicient amounts of the vitamins so that the resulting productin quantities as small orsmaller than 1 cc. contain therein the amountsof the various vitamins as set out hereinabove as being essential tosatisfy a person's daily requirements.

In most cases it will be found that the pH of the vitamin compositionswill be less than about 5.0. This aids in maintaining the stability ofcertain of the vitamins, e. g.. vitamin B1, and it is thereforedecidedly advantageous. The low pH of the compositions may be the resultof various factors. It is well known that vitamin C is an acid andtherefore it is one factor contributing to the acidity; also, if anylactic acid is employed in the composition, it will lower the pHthereof. Furthermore, if synthetic vitamin B1,

i. e., thiamin hydrochloride,"is used instead of a natural concentrateto supply the vitamin B1, it will also aid in giving the vitamincompositions a vitamin compositions which do not contain suflicient ofthe components just mentioned to give the composition a pH of about 5.0or less, it is preferable to add sufficient amounts of citric, tartaric,or some other similar non-toxic organic acid to the composition toadjust the pH thereof to said value. 7

The multl-vitamin compositions prepared as above described may bereadily mixed with aqueous bodies to produce dispersions of the vitaminsin aqueous media. Thus these compositions low pH value. In case it isdesired to prepare may be added to aqueous bodies such as water, to

aqueous food products such as chocolate or other flavored drinks, etc.,and to aqueous medicinal preparations such as tonics. pharmaceuticalsand the like, to form stable products fortified with substantially allof the vitamins. We have found that in order to produce such fortifiedproducts, it is merely necessary to add. the multivitamin compositionsto the milk, coffee, tea,

aqueous bodies with mild agitation, whereby the vitamins are dispersedin the aqueous media; for example, a multivitamin composition preparedas above described may be added with mildagitation to water, milk, skimmilk, fruit juices, coffee, tonics, pharmaceuticals and like, eitherjust prior to consuming the products or at any other suitable time. Inpractically every case the addition of the vitamin composition causesthe immediate formation of dispersions of the vitamins without anyappreciable separation of the fatsoluble vitamins. These dispersionsformed with aqueous bodies ar substantially permanentlystapflofanaqueousbodymt eadditlontheretooithesmallamountofthevitamincomposltion.

remiiredtogivethedesiredvitaminpoteneyto the aqueous medium. Oonseeumtb.the natural characteristics of the aqueous body in this respect will notbe changed. In Preparing vitamincompositionsforthefortiflcationofmlmthspotm ofthe compositionswithrespecttoccrtainvitamins,e.g.,vitaminA,neednotbeashighasinsomeoth'ercasessincemilkitselfcontains appreciable quantities of thesevitamins.

111a multivitamin compositions may be advantageously modified in variousways without aifectingthestabilityoftheflnalproduct. l'br example.natural antioxidant compositions produped by the processes ofapplications of Inran O. Buxton, Serial No. 351,909, filed August 8,1940 now Patent No. 2,345,576, and Serial No. filed June 11, 1941, nowPatent No. 2,345,578, or other suitable antioxidants may be added toenhancethestabilityofthevitaminsAandC. If vitamin E has beenincorporatedinto the multivitamin eompoaition, it will aid instabilizing the vitamins A and 0 against voxidation. Flavoring agents,minerals, \ete., may also be added to the compositions, if desired.

For a fuller understanding of the nature and objects of the invention,reference should be had to the following examples which are given merelyto further illustrate the invention and are not to be construed in alimiting sense.

Ezcample I 200 mgs. of crystalline vitamin B1 were mixed with 2.5 gms.of crystalline vitamin C and 125 ms. of glycerol, and 20 mls. of ethylalcohol were added. on warming slightly, a clear solution resulted. Tothis solution were added 1.1 gins. of a highly potent vitamin Aconcentrate and 0.1 m. of a vitamin 'D concentrate. Sufllcient ethanolto make the solution up to mls. was then half cubic centimeter thereofwas add-ed to a quart of skim milk. No change in the milk could bedetected, andthe pH thereof was the same after adding the vitaminconcentrate as it was before. This amount of the multivitamincomposition was suflicient to bring the vitamin potency of the quart ofmilk up to the average daily adult requirement.

Example [I A completely water-dispersible multivitamin composition wasprepared essentially as in E1- ample I, the principal difference beingthat the 100 mls.

Example III scam: I

product contained 7.5 gills. of glycerol in 19gms.ofglycerolwere assume30 of nicotinic acid amide, and 2 mgs.

Emmie IV Thcmultivitamin composition prepared inthis example difieredfrointhe one infinamplemonhinthatliigmsofiacticacidandusedinsteadof35gms. ofglveerol.

-EmmpleV In this is a vitamin-compositi n wPmparedessentiailythesameaslnplemthe principal diflerenee being that theglycerol was entirely replaced with lactic acid. The flnal wascompletely water-dispersible.

It will be evident irom the above description 1 samples that ourinvention provides amoeess for highly potent, stabie maltivitamincompositions whicheanbedispersed inaqueous bodiestoproduee stable cubiccell of m asawhole.

2. A readily water-dispersible multivitamin composition comprisingethanol. at least one fatsoluble vitamin, riboflavin, at least onewatersoluble vitamin other than riboflavin andalveerlne,theriboflavinbeingpresentinarafloofatleastonemilligrampercubiccentimeterof said dispersible composition asa whole. 1

3. A readily water-dispersible multivitamin composition comprisingethanol, at least one lotsoluble vitamin, riboflavin, at least onewatersoiuble vitamin other than riboflavin and lacticacid,theriboflavinbeins presentinaratioot at least one cubic centimeterof said dispersible composition as a whole.

4.A readily water-dispersible multivitamin' composition comprisingethanol, a vitamin A and D concentrate, riboflavin, niacin, thiamin,vitamincandablendingsolventselectedfromthe group of glyeerine and lacticacid, theriboflavinbeingpresentinaratioofatleast onepercubiccentimetero!saiddispersible composition as a whole.

LORAN OID-BUXI'ON. SOL TOBIAS LIPSIUS.

The following references are of record in the aq eous food nd 1619 ofthis patent: ticals. 38 sineeeertainchangesincarryingouttheaboveUNITEDSI'ATES PATENTS andcertaflntimsintheemm- Number Name Date ositionwhich embody th inv y be 2,175,340 Chesney Oct. 10, 1939 1 made withoutde from its scope. i is i 2,311,554 Lipsius Feb. 16, 1943 tended thatall matter contained in the above de- 35 2 311 517 m t a] 1 943 scnpfions all! e as illustrative and 1,786,095 r H I Dec. 23, 1930 not in a 3 um clam 2,343,254 Dale Mar. 7, 1944 deseri our inven on,w we as new anddesire to secure by Letters Patent is: FOREIGN PATENTS 1. A readily 'n-1:: -1-I- m "m l H131 49 Number Country Date tlon comprising ethanol,least one Iat- 486954 Great Britain May 30, 1938 vi vin, at least onewatersoluble otherthanvinandablendingsolventthegroupco Mam of g ami'ea/ciitheriboflavin 45 can u tieal Association, voL 5,

t in a m0 of at one rilig 11- w D e543,Dec.

hie omntion G Year Supplement to New Mod,

ei'n (1938), p es 94, 153.

